Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study

Bauer, P., Balding, D. J., Klunemann, H. H., Linden, D. E. J., Ory, D. S., Pineda, M., Priller, J., Sedel, F., Muller, A., Chadha-Boreham, H., Welford, R. W. D., Strasser, D. S., Patterson, M. C. and Linden, David ORCID: https://orcid.org/0000-0002-5638-9292 2013. Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study. Human Molecular Genetics 22 (21) , pp. 4349-56. 10.1093/hmg/ddt284

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Abstract

Niemann–Pick disease type C (NP-C) is a rare, autosomal-recessive, progressive neurological disease caused by mutations in either the NPC1 gene (in 95% of cases) or the NPC2 gene. This observational, multicentre genetic screening study evaluated the frequency and phenotypes of NP-C in consecutive adult patients with neurological and psychiatric symptoms. Diagnostic testing for NP-C involved NPC1 and NPC2 exonic gene sequencing and gene dosage analysis. When available, results of filipin staining, plasma cholestane-3β,5α,6β-triol assays and measurements of relevant sphingolipids were also collected. NPC1 and NPC2 gene sequencing was completed in 250/256 patients from 30 psychiatric and neurological reference centres across the EU and USA [median (range) age 38 (18–90) years]. Three patients had a confirmed diagnosis of NP-C; two based on gene sequencing alone (two known causal disease alleles) and one based on gene sequencing and positive filipin staining. A further 12 patients displayed either single mutant NP-C alleles (8 with NPC1 mutations and 3 with NPC2 mutations) or a known causal disease mutation and an unclassified NPC1 allele variant (1 patient). Notably, high plasma cholestane-3β,5α,6β-triol levels were observed for all NP-C cases (n = 3). Overall, the frequency of NP-C patients in this study [1.2% (95% CI; 0.3%, 3.5%)] suggests that there may be an underdiagnosed pool of NP-C patients among adults who share common neurological and psychiatric symptoms.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Oxford University Press
ISSN:	0964-6906
Last Modified:	28 Oct 2022 10:06
URI:	https://orca.cardiff.ac.uk/id/eprint/76746

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